Immune phenotyping of human immune responses to SARS CoV-2 vaccination and infection

摘要 SARS-CoV-2疫苗在创纪录的时间内被开发出来，现在被广泛用于许多不同的领域 世界各地的国家。项目1将重点描述与以下疾病相关的免疫特征 使用不同疫苗类型的SARS-CoV-2免疫。在目标1中，我们将利用现有的 用信使核糖核酸或腺病毒载体免疫前后采集的生物样本 疫苗研究疫苗诱导的抗体反应的持久性和广度，并 确定早期先天免疫如何影响体液和细胞介导的适应性免疫 在接种SARS-CoV-2疫苗后。在目标2中，我们将描述特定的免疫反应 突破性感染，尽管接种了选定病例的深入细胞特征的疫苗 正在经历严重的新冠肺炎。在目标3中，我们还将确定接种疫苗后的免疫反应 感染的个人和经历疫苗相关副作用的个人和 反应性。最后，在目标4中，在人类队列中所做的观察将在人类身上得到验证 原代扁桃体外植体模型系统，通过对这些组织培养物(HC)进行不同的体外处理 疫苗类型，这将使我们能够识别参与疫苗制剂的细胞以及 这些对于建立有效的免疫防御至关重要。对于所有这些研究，标本将是便利的 以临床核心为核心，以免疫表型核心和基因组学为辅助 作为核心，所有产生的数据都将由数据管理和传播核心进行分析。 还将使用不同的技术对来自不同类型的标本的数据进行综合分析 由数据管理和分析核心执行，它将为每个签名确定唯一签名 疫苗平台。总而言之，这些研究将有助于确定 疫苗在SARS-CoV-2免疫背景下诱导免疫保护。

Summary SARS-CoV-2 vaccines have been developed in record time and are now widely used in many different countries around the globe. Project 1 will focus on characterizing immune signatures associated with SARS-CoV-2 immunization using different vaccine types. In Aim 1 we will leverage existing biospecimen collected before and after vaccination with mRNA-based or adenoviral vector-based vaccines to investigate the durability and breadth of vaccine-induced antibody responses and to determine how early innate immune profiles influence humoral and cell-mediated adaptive immunity following SARS-CoV-2 vaccination. In Aim 2 we will characterize the immune responses specific for break-through infections, despite vaccination with in-depth cellular characterization of selected cases experiencing severe COVID-19. In Aim 3 we will also determine the immune responses in vaccinated individuals who get infected and in individuals experiencing vaccine-associated side effects and reactogenicity. Lastly, in Aim 4, the observations made in human cohorts will be validated in the human primary tonsillar explant model system, by treating these histocultures (HC) ex vivo with the different vaccine types, which will allow us to identify the cells that take up the vaccine preparations as well as those critical for mounting efficient immune defenses. For all these studies, specimens will be facilitated by the Clinical Core and with the assistance of the Immune Phenotyping Core and the Genomics Core, all data generated will be analyzed by the Data Management and Dissemination Core. Integrated analyses of data from different types of specimens using different techniques will be also performed by the Data Management and Analysis Core, which will identify unique signatures for each vaccine platform. Collectively, these studies will contribute to defining the biological correlates of vaccine induced immune protection in the context of SARS-CoV-2 immunization.